Comparative efficacy and safety of all kinds of intraocular lenses in presbyopia-correcting cataract surgery: a systematic review and meta-analysis

Purpose To assess the efficacy and safety of various intraocular lenses (IOLs), including standard monofocal, bifocal, trifocal, extended depth of focus (EDOF), and enhanced monofocal IOLs, post-cataract surgery through a network meta-analysis. Methods A systematic search of PubMed, Cochrane Library, and Web of Science was conducted to identify relevant studies from the past 5 years. Parameters such as binocular visual acuities, spectacle independence, contrast sensitivity (CS), and optical quality were used to evaluate efficacy and safety. Data from the selected studies were analyzed using Review Manager 5.4 and STATA 17.0 software. Results Twenty-eight Randomized Controlled Trials (RCTs) comprising 2465 subjects were included. Trifocal IOLs exhibited superior uncorrected near visual acuity (UNVA) compared to monofocal IOLs (MD: -0.35; 95% CI: -0.48, -0.22). Both trifocal (AcrySof IQ PanOptix IOLs group MD: -0.13; 95% CI: -0.21, -0.06) and EDOF IOLs (MD: -0.13; 95% CI: -0.17, -0.09) showed better uncorrected intermediate visual acuity (UIVA) than monofocal IOLs. Trifocal IOLs ranked highest in spectacle independence at various distances (AT LISAtri 839MP group: SUCRA 97.5% for distance, 80.7% for intermediate; AcrySof IQ PanOptix group: SUCRA 83.0% for near). Conclusions For cataract patients who want to treat presbyopia, trifocal IOLs demonstrated better visual acuity and spectacle independence at near distances. Different types of trifocal IOL characteristics differ. EDOF and enhanced monofocal IOLs have improved visual quality at intermediate distances.Therefore, It is very important to select the appropriate IOLs based on the lens characteristics and patient needs. Supplementary Information The online version contains supplementary material available at 10.1186/s12886-024-03446-1.


Introduction
Cataract, characterized by lens opacification, is a leading global cause of blindness and vision impairment [1,2].Particularly prevalent in developing countries, it contributes to vision loss in 33% of visually impaired individuals [3].Approximately 100 million people with moderateto-severe distance vision impairment or blindness could benefit from cataract surgery [4].The current standard of care for significant cataracts is phacoemulsification combined with the intraocular lens implantation [5].However, the increasing variety of lenses pose a significant challenge to ophthalmologists and cataract patients in the clinical choosing.Therefore, it is crucial to assess the function of common IOLs in the clinic.
In the era of increased reliance on electronic devices by middle-aged and elderly individuals, the demand for high-quality vision at intermediate and near distances has surged [6].As a result, the utilization of high-quality IOLs to address pseudo presbyopia has emerged as a significant subject in contemporary cataract surgery practices [7].Beyond standard monofocal IOLs, current clinical practice often involves multifocal IOLs (bifocal and trifocal), EDOF IOLs, and enhanced monofocal IOLs [8][9][10].While standard monofocal IOLs focus light at a single predetermined distance, necessitating additional refractive correction for varying distances [11].In contrast, the mechanism of multifocal IOLs achieve a zooming effect through the use of rings with varying refractive capabilities in different areas of the lens, they can offer superior visual acuity at both near and intermediate distances, along with reduced reliance on corrective eyewear [12][13][14][15].In the earlier stages, the first generation of multifocal IOLs were bifocal, featuring only two optical zones and the subsequent emergence of trifocal IOLs containing three optical zones [16,17].However, they may compromise optical quality, leading to decreased contrast sensitivity, glare, and halo [18,19].EDOF IOLs, endorsed by the American Academy of Ophthalmology, extend the focus area to cover intermediate distances, providing excellent vision for both intermediate and distant ranges.They aim to mitigate the drawbacks of multifocal IOLs, minimizing glare and halos, while cautioning against excessive aberrations that could impact retinal image quality [20,21].Moreover, enhanced monofocal IOLs improves intermediate distance vision by a continuous rise in power from the periphery to the center [22].Therefore it gave better intermediate visual acuity and higher intermediate spectacle independence without impairment of far vision and visual quality, compared to the monofocal IOLs [23].Although enhanced monofocal IOLs and EDOF IOLs share similarities [24], there is currently a lack of comprehensive comparisons among trifocal, enhanced monofocal, and EDOF IOLs.
Existing studies often lack a thorough comparison of commonly used high-quality IOLs.While one report conducted a network analysis of multiple IOLs, it omitted enhanced monofocal IOLs, limiting the comprehensive assessment of visual quality at mid-distance compared to our study [25].Our network meta-analysis specifically targets visual quality at intermediate and near distances, providing a comprehensive analysis of various highquality IOLs.This approach aims to establish a reliable foundation for preoperative patient selection, enhancing postoperative quality of life and satisfaction.The findings of this analysis are expected to encourage the broader adoption of high-quality IOLs in cataract surgery.

Method
This meta-analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), which was registered on Prospero with registration code CRD42023456455 [26].

Inclusion criteria
Articles meeting the following criteria will be included in conducting the study: (1) Study subjects.Participants underwent cataract surgery in both eyes and had the same IOL implanted in both eyes, and all participants were older than 40 years of age.( 2

Exclusion criteria
Articles that met the following criteria were excluded: (1) duplicated studies, conference abstracts, letters, review, animal studies or research in vitro.(2) single-arm design studies.(3) cataract surgery in only one eye.(4) different types of IOLs implanted in both eyes.(5) patients had severe irregular astigmatism.(6) patients had ocular pathology that could affect the visual function, history of ocular trauma or prior ocular surgery and IOL centering, intraoperative or postoperative complications and systemic disease.

Data extraction and quality assessment
Among the included studies, two researchers (J.Y.L. and Y.X.Z.) independently extracted the data.Any discrepancies will be resolved by consensus and, if harmonization is not possible, a third examiner will be consulted for arbitration.We accessed the quality of the included randomized controlled studies using Review Manager 5.4.1 according to the Cochrane risk-of-bias assessment tool.The preoperative data collected included name of the first author , publication year, sample size, sex, age, follow-up time, interventions.Essential data for the included studies have been extracted and presented in the Table 1.

Primary and secondary outcomes
The primary outcomes included corrected and uncorrected binocular visual acuities (distant, intermediate and near visual acuity), spectacle independence (distant, intermediate and near spectacle independence).The secondary comprehensive endpoints included optical quality (holas and glare) and contrast sensitivity (under photopic and mesopic conditions).Primary outcomes are used to evaluate validity and secondary outcomes are used to evaluate safety.

Statistical analysis
The mean difference (MD) and its 95% confidence interval (CI) were used to evaluate the effects of the outcomes for continuous variables, and the odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the effects of the outcomes for dichotomous variable.The entire analysis was performed using the random effects model.Conducting network meta-analyses within Stata software (version 17.0), we executed data processing, generated network evidence plots, performed an inconsistency test, ranked interventions using the Surface Under the Cumulative Ranking (SUCRA), created forest plots, and analyzed funnel plots.Network evidence plots visually depicted treatment comparisons for each outcome, and the inconsistency test evaluated metric coherence (with p < 0.05 indicating significant inconsistency).It's crucial to emphasize that SUCRA is integral to these analyses.SUCRA ranks intervention efficacy based on cumulative probability, with higher values (closer to 1) signifying greater effectiveness.Serving as a valuable tool, SUCRA summarizes and interprets relative intervention efficacy across diverse outcomes in network meta-analyses.Forest plots aided in pairwise comparisons (a result of 0 denoting no significant difference), and potential publication bias was explored through a funnel plot.

Corrected visual acuity
The corrected visual acuities yielded a tendency similar to that seen in the uncorrected outcomes.Distant and near visual acuity formed two closed loops and intermediate visual acuity formed three according to the evidence network (Fig. 2d-f

Spectacle independence
There were 11 studies reported spectacle independence.We studied spectacle independence separately for distant, intermediate and near distances.All three indicators form three closed loops according to the network evidence (Fig. 2g-i

Contrast sensitivity (CS)
We reported the result of contrast sensitivity under both photopic and mesopic conditions and collected data at spatial frequencies of 3, 6, 12, and 18 cycles per degree (cpd).Their network relationship is shown in Supplementary Fig. 1 (a-h).Ranking the effectiveness of all IOLs by SUCRA results, at the four spatial frequencies, the SUCRA values for monofocal and enhanced monofocal IOLs are consistently in the top, the values for bifocal and AT LISAtri 839MP IOLs are consistently in the bottom under both photopic and mesopic conditions, besides, the contrast sensitivity of FineVision POD F IOLs group gradually improves with increasing spatial frequency (Supplementary Fig. 2a-h).Under photopic condition, when a comparison is made between two IOLs, monofocal and enhanced monofocal IOLs showed better CS than bifocal IOLs and AT LISAtri 839MP IOLs at the four spatial frequencies (Supplementary Fig. 3a-d).At spatial frequencies of 12 cpd, FineVision POD F IOLs were more effective than bifocal (MD 0.20, 95% Cl 0.02, 0.39) and AT LISAtri 839MP IOLs (MD 0.21, 95% Cl 0.04, 0.38) (Supplementary Fig. 3c).At spatial frequencies of 18 cpd, FineVision POD F IOLs were more effective than AT LISAtri 839MP IOLs (Supplementary Fig. 3d).Under mesopic condition, monofocal and enhanced monofocal IOLs more significantiy effective than bifocal, AT LISAtri 839MP, AcrySof IQ PanOptix, other new trifocal and EDOF IOLs at spatial frequencies of 3 cpd (Supplementary Fig. 3e) and 6 cpd (Supplementary Fig. 3f ).CS of some multifocal IOLs becomes progressively higher with increasing spatial frequency (Supplementary Fig. 3g, h), especialiy FineVision POD F IOLs were more effective than other groups at spatial frequencies of 18 cpd (Supplementary Fig. 3h).

Halos and glare
Halos and glare are two of the most common visual impairments that patients experience after multifocal IOL surgery.The network evidence showed a total of 7 closed loops for halos and 4 closed loops for glare (Supplementary Fig. 1i, j 3i).Besides, in the ordering of the areas under the curve, other new trifocal IOLs (SUCRA 71.3%) and AT LISAtri 839MP IOLs (SUCRA 68.9%) rank in the first two in glare (Supplementary Fig. 2j).For the pairwise meta-analysis, none of the results of the comparisons between the various interventions were significantly different from each other (Supplementary Fig. 3t).

Publication bias and quality assessment
The funnel plot of this study revealed that most of the scatter points were located on both sides of the vertical line.They were basically symmetrical and may have had a certain degree of publication bias.The funnel plot of the effect on visual outcome after implantation of eight types of artificial lenses in both eyes is presented in Supplementary Fig. 4 (a-i) and Supplementary Fig. 5 (a-j).Based on risk of bias assessment, there were two randomized clinical trials showed a low high of bias due to inadequate sequence generation.Regarding allocation concealment, one trial had a high risk and two trial did not mention.Three trials were not blinded to participants and personnel, while two were not blinded to outcome assessment.In all randomized clinical studies, the likelihood of selective reporting bias and incomplete outcome data was minimal.In all included trials, other biases mostly unclear.Therefore, the overall quality of the incorporated articles is high, respectively, Fig. 5 and Supplementary Fig. 6 show the risk-of-bias summary and risk-of-bias graph for selected studies.The results of the consistency analysis across the study indicators can be seen in Table 2, in performing the consistency test, we found that UNVA and CNVA were less consistent, the other indicators were more consistent, and there were no significant differences between direct and indirect comparisons.The League tables are shown as mean and 95% CIs to assess whether there was a signifcant diference in the efcacy or safety of each regimen (Supplementary Table 1).

Discussion
This study represents the first attempt to comprehensively compare the efficacy and safety of different IOLs for presbyopia-correcting cataract surgery using a network meta-analysis based on a frequency-based framework.The primary objective was to provide a credible evidence-based medical foundation for choosing clinical IOLs.The results of our network meta-analysis are promising.Initially, we assessed the efficacy of different IOLs.For binocular UNVA and CNVA, statistical differences were observed when comparing multifocal and EDOF IOLs to monofocal IOLs, with trifocal IOLs demonstrating the best near visual acuity, consistent with previous research [56].A comparison between AT LISA tri 839MP and EDOF IOLs in near vision revealed no significant difference, contrary to another study, possibly due to our inclusion of four groups of trifocal IOLs with different designs [36].Trifocal IOLs ensure vision at three distances through light distribution, with more light distribution resulting in better vision [57].All four trifocal IOLs groups had distinct light distributions at near distances, with AT LISA tri 839MP IOLs, a conventional trifocal IOLs, having only 30% light distribution at near distances [57].The ranking of UNVA area under the curve revealed the largest share for the other new trifocal IOLs.In a comparison with Acrysof PanOptix, the new trifocal IOLs displayed extensive vision, particularly at near distances, and superior mesopic performance in cataract surgery patients [58].Regarding binocular UIVA and CIVA, a Cochrane database evaluation from 2020 found that trifocal IOLs implantation resulted in better UIVA at one year, without a significant advantage for uncorrected near and distance vision [59].A subsequent 2023 evaluation, expanded in patient age range, confirmed these findings [10].Additionally, EDOF IOLs, with an achromatic diffractive surface provide a low add foci, extending the range of vision from distance through intermediate, a study with a three-month follow-up, found EDOF IOLs to be a well-tolerated option for correcting far and intermediate vision [60].In our study, compared to most trifocal IOL groups, EDOF IOLs exhibited better UIVA, but trifocal IOLs showed a more significant advantage in CIVA.Enhanced monofocal IOLs, a recent introduction, demonstrated advantages in intermediate distance vision.However, compared to EDOF IOLs, the latter showed superior near vision outcomes with a higher rate of spectacle independence [24].Monofocal IOLs are designed for clear vision at the retinal plane, providing detailed and high-contrast vision for distant objects [61].Our results also indicate that other IOL types were not as effective as standard monofocal and enhanced monofocal IOLs for binocular UDVA and CDVA.
Postoperative changes in refractive power often necessitate customized fine-tuning to optimize spectacle independence for patients [62].In our literature review, there was no mention of spectacle independence for enhanced monofocal IOLs.Therefore, we compared seven types of IOLs for this indicator, finding that other IOLs exhibited superior spectacle independence compared to monofocal IOLs at both intermediate and near distances.At intermediate distances, there was no significant difference between EDOF and trifocal IOLs.However, at near distances, trifocal IOLs demonstrated more pronounced spectacle independence.A clinical report by Schallhorn on cataract patients indicated that EDOF IOLs achieved 83.6% spectacle independence for near vision and 95.4% for distance vision [63].Another study comparing presbyopia-correcting IOLs reported that 71-96% of patients achieved spectacle independence, with the EDOF group showing a lower percentage than the trifocal group [64].In our spectacle independence ranking, AT LISAtri 839MP IOLs secured the top position at all three distances.AcrySof IQ PanOptix IOLs claimed the second spot for intermediate and near spectacle independence, while the EDOF IOLs group ranked third for spectacle independence at intermediate distances.Rita Mencucci's study on AT LISAtri 839MP IOLs reported that 33% of trifocal IOL patients and 40% of EDOF IOL patients needed reading glasses for some activities, aligning with our findings [65].
While our current study suggests that trifocal IOLs are the most effective, this conclusion may not be definitive.Multifocal IOLs were designed to split light into different focal points.However, the neuro-adaptive process required to process these different images can be time-consuming and frustrating for patient [66].Therefore, we examined the safety of various IOLs in terms of optical quality, focusing on CS, halos, and glare.In terms of CS, significant decreases were observed in other IOL groups compared to monofocal and enhanced monofocal IOLs under both photopic and mesopic conditions, with bifocal and AT LISAtri 839MP IOLs exhibiting the most noticeable effects.The CS of both EDOF and FineVision POD F IOLs increased with frequency, and EDOF IOLs have better CS only at lower spatial frequencies, with no significant difference at higher spatial frequencies, in line with previous reports [67,68].This aligns with the findings of an RCT related to a multifocal IOL reported by Gil, MÁ in 2022 [69,70].Preethi Karuppiah's report comparing trifocal and EDOF IOLs also indicated better CS in EDOF IOLs [70].Regarding halos, the monofocal and enhanced monofocal IOLs group exhibited fewer halos, with no statistically significant differences among other high-quality IOL groups.For glare, no statistical differences were found when comparing all groups, potentially due to the limited number of included studies.Multifocal IOLs are reported to have more pronounced optical phenomena such as halos and glare compared to monofocal IOLs in most studies [71,72].A meta-analysis by Sumitra in 2019 comparing multifocal IOLs and standard monofocal IOLs supported our study's findings, indicating a greater risk of adverse visual phenomena with multifocal IOLs [56], A report by Leyla Asena found less optical interference and visual impairment in patients after bilateral implantation of EDOF IOLs than trifocal IOLs, and we supporting this result [73].
Posterior Capsular Opacification (PCO) is a common complication following cataract surgery and can impact visual outcomes by causing distortion and loss of corrected visual acuity.Clinically significant PCO requiring Nd: YAG capsulotomy adversely affects visual acuity.In Jorge's study, during the 3, 6, and 12-month follow-ups, the ReSTOR group had 6 patients (17.6%) requiring Nd: YAG capsulotomy, and the bifocal AT LISA group had 3 patients (8.8%) at the 12-month follow-up only [27].Another study by Bilbao-Calabuig suggested that AT Lisa 839 IOLs takes longer for PCO development compared to FineVision IOLs [74].Decentration and tilt are also common complications of cataract surgery.They increase high-order aberrations and reduce visual quality.Different IOLs have varied effects on visual quality due to postoperative decentration and tilt.Aspheric and multifocal IOLs are more susceptible to decentration and tilt compared to other types of IOLs [75].Research indicates that decentration and tilt have more pronounced effects on refractive multifocal IOLs than diffractive multifocal IOLs, and more pronounced effects on EDOF IOLs than refractive and diffractive multifocal IOLs [76].The above complications are also common complications after cataract surgery, but due to the lack of data support, we did not conduct in-depth research, but this also provides a new direction for our future research.
Our study presents a comprehensive assessment of the effectiveness of different IOLs, making it the largest network meta-analysis of RCTs to date.The analysis covers the safety and efficacy of the most common IOLs across various healthcare institutions, offering valuable guidance for patients in selecting the most suitable IOLs and enhancing postoperative satisfaction.The study highlights the importance of analyzing individual preoperative conditions and overall physical status when choosing an IOL, taking into account financial considerations and lifestyle needs.However, out network meta-analysis has certain limitations.Firstly, the inclusion of 28 RCTs introduces variability due to the lack of detailed methodological information in some studies.Bias concerns related to randomization were addressed through bias analyses, and efforts were made to standardize study protocols.Secondly, discrepancies in measurements, criteria, and patient inclusion among different RCTs could contribute to bias.Inconsistent definitions of proximal and intermediate measurements were identified as a primary reason for bias in the assessment of uncorrected and corrected near and intermediate visual acuity.Thirdly, the relatively short follow-up times in the included RCTs and limited studies on postoperative complications, such as capsule fibrosis, YAG rates, and decentration, may affect the completeness of the analysis.Although you attempted to collect and analyze data on postoperative complications and patient satisfaction through questionnaires, variations in questionnaire topics and evaluation criteria hindered uniform categorization.Despite these limitations, our study contributes valuable insights into the field of cataract surgery and IOL selection, emphasizing the need for further research and individualized analysis of patient situations.

Conclusion
In conclusion, the results of the network meta-analysis showed that various different IOLs were compared with each other and it was found that for patients with bilateral cataracts, binocular implantation of trifocal IOLs(especially AcrySof IQ PanOptix TFNT00 and FineVision POD FT IOLs) can give higher spectacle independence and good vision at intermediate and near distances, but need to overcome the decrease of optical quality, and EDOF and enhanced monofocal IOLs are also a good choices if there are more activities in daily life at intermediate distances.At the same time, enhanced monofocal IOLs are a better option for patients who are sensitive to decreased visual quality.However, more high-quality, large-sample, multicenter, randomized, double-blind trials are needed to confirm the reliability of the findings.The optimal treatment regimen should be determined on an individual patient basis, safety outcomes, and patient and caregiver decisions.
) Intervention measures.Patients in the control group were implanted with standard monofocal IOLs in both eyes.Patients in the treatment group had other types of IOLs implanted in both eyes, including: bifocal IOLs, trifocal IOLs (AT LISAtri 839MP, FineVision POD F, AcrySof IQ PanOptix and other new trifocal IOLs), EDOF IOLs, and enhanced monofocal IOLs.(3) Outcome indicator.All literature covered should report on one or more primary or secondary indicators.The primary outcome indicator were visual acuity, spectacle independence and optical quality.The secondary outcome indicators were as follows: contrast sensitivity (CS) (under photopic and mesopic conditions).(4) Study type.The included studies were RCTs.

Fig. 5
Fig. 5 Risk of bias summary